System for continuous measuring, recording and monitoring of the splanchnic tissue perfusion and the pulmonary physiological dead space, and use thereof

ABSTRACT

The present invention relates to a new system for measuring, recording and monitoring the splanchnic tissue perfusion and the pulmonary physiological dead space in an automated way, both continuously and intermittently, and in real time, which is easy to manage and generates information easy to interpret. Said system comprises at least four measuring devices of medical parameters, connected to a device receiving, converting, storing, integrating, processing, and allowing the management and display of the data recorded in the measurements and the parameters estimated by the same. For this purpose, said device comprises a specific computer program of estimation of parameters related to the measurement of the splanchnic tissue perfusion and the pulmonary physiological dead space, from the data derived from the measuring devices. Likewise, the present invention is related to the use of a device for measuring, recording and monitoring of the splanchnic tissue perfusion and the pulmonary physiological dead space.

FIELD OF THE INVENTION

The present invention is comprised in the field of medicine, specifically of intensive care and major surgery, particularly for the diagnosis of occult shock.

BACKGROUND OF THE INVENTION

Faced with an inadequate supply of oxygen, the cell uses anaerobic glycolysis in an attempt to maintain the normal cell function, causing an accumulation of lactic acid and the release of hydrogen ions derived from ATP hydrolysis, causing a decrease in the pH of the tissue (see Bibliographic Reference (1)). Thus, the early changes in the pH of the tissue are useful for assessing the oxygenation of that tissue and the status of its microcirculation (2).

In the critically ill patient, when compensatory mechanisms fail to maintain a suitable oxygenation in all tissues, the neurohumoral response of the organism causes a redistribution of the blood flow aimed at preserving the function of “noble organs” such as the brain and the heart, at the expense of decreasing the infusion of “non-vital organs” such as the skin and splanchnic territory (3). Unlike the skin, the splanchnic territory, and particularly the intestinal mucosa, has high metabolic needs that along with certain anatomical characteristics that make it particularly susceptible to hypoxia, account for the intestine being the first organ to be affected in situations of hypoperfusion/hypoxia, and the last one to recover (2, 4). Therefore, the assessment of the tissue oxygenation at this level by monitoring the gastric intramucosal pH (pHi), will allow us to detect these situations early and prevent further worsening thereof, as well as to guarantee full recovery after an obvious shock episode (2, 4, 5).

The pHi can be measured by a microelectrode inserted in the gastric mucosa, but the invasiveness of the method, the impossibility of in vivo recalibration and frequent detachment of the electrode, make it impractical in the clinic (6). Therefore, we turn to the indirect measurement of pHi, based on the principle of tonometry, by which the gases diffuse freely through the tissues. Thus, in 1959 Boda and Murányi (7) made an estimate of the arterial PCO₂ in more than 400 children mechanically ventilated for poliomyelitis, using a tonometry probe similar to the current ones, and inserted in the stomach through the nose. Their clinical experience led them to conclude that: 1) The arterial CO₂ tension can be estimated with reasonable accuracy with the gastrotonometric method. 2) In patients in severe shock situation the PCO₂ in the tonometer may be deceptively high. However, they do not understand the reason for this after fact. These results were subsequently confirmed by Bergofsky (8) by demonstrating that the fluid in the lumen of a hollow organ (urinary bladder, gallbladder, stomach), balances the tension of the gases (PO₂ and PCO₂) with that of the cells and tissues containing thereof, and these in turn with that of the blood irrigating thereof. And simultaneously also by Dawson (9) that observed in experimental animals how the PO₂ and the PCO₂ measured in the saline serum instilled in intestinal pouches experienced changes proportional to those of the blood. Therefore, the measurement of the CO₂ Pressure in the gas in the lumen of the intestine is equivalent to the CO₂ Pressure in the intestinal mucosa (10).

In 1982, Fiddian-Green et al (11) use these findings for postulating that the intestinal mucosa pH can be calculated in an indirect way. This hypothesis is based on two assumptions: 1) The PCO₂ tonometrically measured approximates to that of the intestinal mucosa, since the CO₂, for its high diffusion capacity, quickly reaches the balance between the tissue and the intraluminal lumen. 2) The bicarbonate concentration in the intestinal mucosa is in balance with that of the intestinal capillary bed, and this in turn, with that of the arterial blood (1). Therefore, the pHi calculation can be performed by a modification of the Henderson-Hasselbalch equation: pHi=6.1+log 10([HCO₃ ⁻]/PgCO₂*0.03)  Equation 1

Wherein 6.1 is the pK of the HCO₃ ⁻/CO₂ system in plasma at 37° C.; [HCO₃ ⁻] is the arterial concentration of bicarbonate (mM/L); PgCO₂ is the PCO₂ of the tonometry probe set to the equilibrium time; 0.03 is the solubility constant of the CO₂ in plasma at 37° C.

Thus, the deceptive PCO₂ increases of the stomach in relation to the arterial PCO₂, observed by Boda and Murányi in patients in situation of severe shock, would correspond to pHi drops as a result of regional tissue hypoperfusion. Grum et al, in 1984 develop a tonometry probe constituting the basis of the current commercial equipments. Using this equipment in dogs, they observed how the pHi remained constant as long as the blood flow was maintained above a critical value. Below this the pHi decreased. Moreover, these decreases in the pHi were accompanied by decreases in the O₂ consumption. In 1990 Antonsson et al (6) validate the technique in an experimental model, by comparison of the tonometrically calculated pHi with that obtained from microelectrodes implanted directly in the mucosa of the stomach.

Classically, 2 other derived parameters have been used. To calculate them the arterial pH values (pHa) are used, obtained with the analysis of an arterial blood sample and the pHi, calculated by equation 1. Difference of pH or pHgap=pHa−pHi  Equation 2 Standard intramucosal pH or pHis=7.4−pHgap  Equation 3

According to the place where the measurement of the CO₂ in the lumen of the digestive tube (PgCO2) is performed, 2 types of measurement are distinguished:

1) Tonometry with CO₂ analysis outside the organism: the technique consists of the placement of a nasogastric tube provided with a terminal silicone balloon permeable to CO₂ that is left accommodated in the stomach. It is radio-opaque to facilitate its correct location by X-ray (Rx). It is therefore a minimally invasive technique. The analysis requires the extraction of the samples in order to be analysed. There are two types depending on the medium with which the balloon is filled:

A. Tonometry with physiological saline serum (PSS): it is the technique initially used and with which more experience is available. Thus, most of the studies that have evaluated its usefulness have been based on it. The technique requires, however, great user experience to obtain reliable results (12). The process of measuring can be divided in 2 times:

-   -   1. Measurement of the PgCO₂: prior to the insertion of the         catheter a careful purging of the balloon with PSS must be         performed, to remove the air it may contain. After its insertion         it is filled with 2.5 mL of the same serum, that is maintained         over an equilibrium period (30 minutes minimum), that has to be         known in case of being of less than 90 minutes, so that the         correction is made. When extracting the sample the first mL must         be discarded, corresponding to the dead space in the catheter,         it must be preserved anaerobically (sealed) and processed         immediately to be reliable. The measurement is performed in a         standard blood gas analyzer, although there have been         objectified important differences between different models,         probably as a function of the calibration (it is performed for         blood samples, not for PSS), so that each centre has to         determine its reference values (2).     -   2. Calculation of the pHi and related parameters: in order to         calculate an arterial blood extraction must be performed. With         this sample the arterial pH and PCO₂ measurements are obtained         in a standard blood gas analyzer. Using these measurements the         analyzer itself performs the calculation of the arterial         bicarbonate (HCO₃ ⁻) that along with the PgCO₂ obtained from the         tonometry probe allow the calculation of the pHi according to         Equation 1. This calculation along with the measurement of the         arterial pH, allow the calculation of the pHgap and pHis         according to Equations 2 and 3.     -   A value of pHi<7.31 is generally considered abnormal (13).         Therefore, the tonometry technique with saline serum is too         cumbersome, requires user experience, is little reproducible and         does not provide continuous information. For these reasons,         although it has proved to be useful in research studies, it has         not been introduced as a usual monitoring technique in         critically ill patients. Currently, these probes are no longer         marketed.

B. Tonometry with air: to overcome some of the limitations of the tonometry with saline, the Datex-Ohmeda company adapted a capnograph (Tonocap®) that automatically filled the balloon with air, extracting the same periodically (every 10 minutes) to perform the measurements of the PgCO₂. The technique was validated by several authors (14-16). Subsequently, an improvement in this equipment, the M-Tone Module of the same manufacturer (currently belonging to the General Electric group) was marketed. These equipments automate the measurements of the PgCO₂, but for the calculation of the pHi it is still required to perform intermittent blood extractions that must be analyzed in a standard blood gas analyzer, and the results thereof entered manually in the apparatus. Therefore, although part of the measurement process has been automated, the technique continues to be intermittent and cumbersome.

To mitigate these disadvantages, the use as an indicator of tissue hypoperfusion of a related regional parameter has been proposed, the gastric-arterial CO₂ gradient or CO₂gap can be calculated as follows: CO₂gap or P(g−a)CO₂=PgCO₂−PaCO₂  Equation 4

Wherein PaCO₂ is the CO₂ arterial pressure. This parameter also requires the performing of intermittent blood extractions to obtain the PaCO₂. Therefore, the PCO₂gap is not measured continuously either. However, the manufacturer has incorporated in the equipment a second capnograph to measure continuously the CO₂ end-expiratory pressure (EtCO₂), as a way of approximation to the PaCO₂, since in normal conditions the EtCO₂ is related to the PaCO₂ (the difference between both measurements in healthy volunteers is usually of 2 to 5 mmHg). Thus, it performs in an automated and continuous way, the calculation of a new derived parameter: the gradient between the gastric and expiratory CO₂: CO₂gap(et) or P(g−Et)CO₂=PgCO₂−EtCO₂  Equation 5

However, the connection between the PaCO₂ and the EtCO₂ is lost frequently in the critically ill patient (target patient for the implementation of this monitoring). For this reason, the integration of these two parameters has not proven clinical usefulness and the device has fallen into disuse. Still, this equipment and its sampling probes are still marketed by the Datex-Ohmeda company and are available at an international level.

Moreover, the Datex Ohmeda S5 multiparametric system, with M-Tone tonometry module and capnograph for the measurement of the EtCO₂, only provides a numerical value of the latest measurement. It does neither represent the data graphically nor does it show trends facilitating the interpretation of the data and assessing its evolution over time.

2) Tonometry with CO₂ “in situ” analysis: the measurement of the CO₂ in the lumen of the stomach (PgCO2) can be performed “in situ” and in real time by the placement of a fiber optic sensor. This sensor has been developed by The Institute of Chemical Process Development and Control. It has been applied in healthy volunteers and in intensive care patients. However, for this parameter to have clinical usefulness its integration with other systemic variables allowing the calculation of derived regional parameters is necessary. This device offers only this measurement, so it has little clinical usefulness.

As we have seen, the indirect calculation of the pHi or the CO₂gap requires intermittent blood extractions to be obtained in order to obtain the bicarbonate or the PaCO₂, along with the measurement of the PgCO₂. The technique, therefore, is cumbersome and does not provide continuous information, which seriously limits its clinical use. Moreover, the attempt of integration for continuous measuring of the M-Tone Module has not resulted effective so far.

The system described herein overcomes the important limitations of the instruments currently in use, mainly the M-Tone Module of the Datex-Ohmeda company (currently belonging to the General Electric group). Additionally, the present system can estimate in a continuous and automated way the pulmonary physiological dead space in the critically ill patient.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 depicts a scheme of the system for measuring, recording, and monitoring the splanchnic tissue perfusion and the pulmonary physiological dead space in an automated way, both continuously and intermittently, and in real time (pH-Tone instrument).

FIG. 2 depicts a chart showing variation of the %CO₂gap, pHis and pHgap at different levels of PaCO₂ with a constant CO₂gap of 10 mmHg.

FIG. 3 depicts an illustrative scheme of a patient in intensive care, resuscitation, or operating room with a tonometry probe for the measurement of PgCO₂ and a sensor for the earlobe for the measurement of PtcCO₂, wherein the probe for the measurement of EtCO₂ is found at the end of the endotracheal tube.

FIG. 4 depicts a simulation of the output interface (f7) of the device (f) of reception, conversion, storage, integration, processing, management and display of the data recorded in the measurements, allowing the user to view in real time the information input in the device (f) and output from the computer module (f5), in both tabular and graphic form.

FIG. 5 depicts a graph showing a 48 hours evolution of the standard pHi (pHis) in its three forms of calculation in a patient with ARDS: pHis Sample: calculated intermittently with the measurement of the PaCO₂ obtained from a blood sample; pHis(tc): determined in a continuous and automated way with the measurement of the transcutaneous CO₂ (present invention); and pHis(et): determined in a continuous and automated way with the measurement of the CO₂ exhaled (present invention).

DESCRIPTION OF THE INVENTION

The present invention relates to a new system for measuring, recording and monitoring the splanchnic tissue perfusion and the pulmonary physiological dead space in an automated way, both continuously and intermittently, and in real time, which is easy to manage and generates information easy to interpret.

The system object of the present invention comprises at least (FIG. 1):

a) a continuous measuring device of the carbonic anhydride pressure in the lumen of the digestive tube (PgCO₂). This device includes a probe the positioning of which can be performed nasogastrically or recto-sigmoidally. The CO₂ measurement can be performed by two types of probes:

-   -   Probe with terminal silicone balloon permeable to CO₂ that is         filled with air: the measurement of the CO₂ is performed in the         apparatus (capnograph) by the extraction, analysis and         reintroduction of the gas sample in the balloon, in an         intermittent (every 10 minutes) and automated way, as the         General Electric M-Tone Module, or another one that might be         marketed.     -   Probe with a fibre optic sensor in its patient end: “continuous         measuring in situ”, as the developed by The Institute of         Chemical Process Development and Control, or other that might be         marketed.

b) a standard intermittent measuring device of the arterial pH (pHa) and CO₂ arterial pressure (PaCO₂) of a blood sample;

c) a continuous measuring device of the CO₂ transcutaneous pressure (PtcCO₂) consisting of a transcutaneous capnography sensor; and

d) a continuous measuring device of the end-expiratory CO₂ (EtCO₂) consisting of an expiratory air standard capnograph, the probe or sensor of which is connected to the patient's airway;

e) specific connections between the enumerated measuring devices (a, b, c and d) and an f) device. These connections are preferably made in the devices a, c and d through the RS-232 serial ports thereof, and in device b, through its network connection (Ethernet), since its location is usually remote.

f) a device of reception, conversion, storage, integration, processing, management and display of data recorded in the continuous, automated and real-time measurements.

The device (f) of reception, conversion, storage, integration, processing, management and display of data recorded in the measurements comprises at least the following elements:

-   -   a computer program module (f1) of reception and storage of the         measurements performed with the measuring devices (a, b, c and         d),     -   a second specific module (f2) of conversion-normalization of the         data received and stored in the module (f1) of reception and         storage,     -   a third module (f3) of processing and integration of the data         normalized by the normalization module (f2),     -   a fourth program module (f4) of storage of the data processed by         the processing module (f3);     -   a fifth specific module (f5) of automated, continuous and real         time estimate of the parameters related to the measurement of         the splanchnic tissue perfusion and the pulmonary physiological         dead space, from the data derived from the 4^(th) storage module         (f4) that have been previously processed by the processing         module (f3);     -   an input interface (f6) allowing the user to enter commands in         the computer program (f5) of parameter estimate, as well as         additional data;     -   an output interface (f7) allowing the user to view in real time         the information input in the device (f) and the output from the         computer module (f5), in both tabular and graphic form;     -   an eighth module (f8) for recording the parameters estimated by         the module (f5), for the subsequent recovery and analysis         thereof; and     -   an alarm (f9) for checking the operation of the device (f) and         the specific connections (e), to detect problems in operating         and receiving measurements, and parameters programmable alarm         (measurement values exceeded) by the module (f5), independent of         that existing in the measuring equipment.

The parameters related to the measurement of the splanchnic tissue perfusion and the pulmonary physiological dead space calculated by the estimate computer program (f5) are the following:

-   -   CO₂ arterial pressure (PaCO₂), which is measured intermittently         by the device (b) or is estimated continuously as a function of         the PtcCO₂;     -   difference of systemic-regional pH (pHgap), which is estimated         as a function of the PgCO₂ and the measured PaCO₂;     -   intramucosal pH in the digestive tube (pHi), which is estimated         as a function of the pHa, the PgCO₂ and the measured PaCO₂,     -   standard intramucosal pH (pHis) which is estimated as a function         of the normal arterial pH, the PgCO₂ and the measured PaCO₂, the         normal arterial pH being 7.4.     -   gradient between the pressures of gastric CO₂ and arterial CO₂         in % (% CO₂gap), which is estimated as a function of the PgCO₂         and the measured PaCO₂;     -   gradient between the pressures of gastric CO₂ and transcutaneous         CO₂ in % (% CO₂gap(tc)), which is estimated as a function of the         PgCO₂ and the PtcCO₂;     -   difference of transcutaneous-regional pH (pHgap(tc)), which is         estimated as a function of the PgCO₂ and the PtcCO₂;     -   transcutaneous standard intramucosal pH (pHis(tc)), which is         estimated as a function of the normal arterial pH, the PgCO₂ and         the PtcCO₂;     -   difference of the arterial-respiratory pH (pHgap(a-et)), which         is estimated as a function of the measured PaCO₂ and the EtCO₂;     -   arterial-respiratory standard pH (pHs(a-et)), which is estimated         as a function of the normal arterial pH, the measured PaCO₂ and         the EtCO₂;     -   pulmonary physiological dead space, V_(D)/V_(T), which is         estimated as a function of the PaCO₂ obtained by the device (b)         and the PECO₂ obtained by the device (d);     -   transcutaneous pulmonary physiological dead space         (V_(D)/V_(T)(tc)), which is estimated as a function of the         PtcCO₂ and the EtCO₂;     -   difference of transcutaneous-expiratory pH (pHgap(tc-et)), which         is estimated as a function of the PtcCO₂ and the EtCO₂; and     -   transcutaneous-expiratory standard pH (pHs(tc-et)), which is         estimated as a function of the normal arterial pH, the PtcCO₂         and the EtCO₂.

Preferably, the measuring device (a) of the carbonic anhydride pressure in the lumen of the digestive tube is the M-Tone Module of the Datex company, which allows the obtainment of the measurement in an automated way every 10 minutes. In a particular embodiment, the device (a) would be constituted by a Datex Ohmeda S5 multiparametric system with an M-Tone tonometry module and tonometry probe output. The information depicting media in this system show the values of PGCO₂, EtCO₂ and the difference between them P(g-Et)CO₂, rounding off decimals, as well as the scale of time between PgCO₂ measurements. However, it only provides the numerical value of the latestmeasurement, neither does it represent the data graphically nor does it show trends facilitating the interpretation thereof and assessing its evolution over time.

Preferably, the pHa and PaCO₂ values measured by the device (b) of the intermittent blood samples are entered after the analysis either manually through the keyboard or received in an automated way through the Ethernet connection.

The selection of the CO₂ transcutaneous pressure measurement (PtcCO₂) is due to the fact that it can be performed continuously and bloodless, and it is the one that approximates the closest to the real value of the CO₂ arterial Pressure (PaCO₂). The measurement of this parameter has not been used previously for the purpose of assessing splanchnic tissue perfusion. Preferably, the transcutaneous capnography sensor of the device (c) is a transcutaneous oxycapnograph for the earlobe. In a particular embodiment, the transcutaneous oxycapnograph for the earlobe is the “Tosca” model of the Radiomether company, comprising 2 sensors, a pulsoxymeter not used in the present invention, and a transcutaneous capnograph (sensor employed in the present invention), since it can be used in patients of any age. Although other manufacturers, such as Sentec, have similar equipment. The Radiomether Tina model can also be used, or any other one.

On its side, the CO₂ end-expiratory measurement (EtCO₂) has the main purpose of estimating, both intermittently (with the PaCO₂ measurement) and continuously (with the PtcCO₂ measurement), the pulmonary physiological dead space. The continuous estimate has not been described so far in the literature. This measurement can be obtained with any expiratory air capnograph; there are many manufacturers of this device. Preferably, if the patient is intubated, the EtCO₂ measuring probe is attached to the end of the endotracheal tube.

Preferably, the parameter estimate computer program (f5), the device (f) of reception, conversion, storage, integration, processing, management and display of the data recorded in the measurements, performs the following calculations:

-   -   Intermittent calculation of parameters for assessment of the         splanchnic perfusion: the measurements obtained by the         devices (a) and (b) are employed. These calculations have been         the ones classically used. However, our invention, unlike other         systems, does not employ the usual equations mentioned in the         State of the Art section, but simplified equations, in addition         to providing a new parameter, the CO₂gap in percentage (%         CO₂gap):     -   Gastric or sigmoidal intramucosal pH (pHi), from the difference         between the pHa and the logarithm of the ratio between the PgCO₂         and the PaCO₂ measured, expressed by the formula         pHi=pHa−log PgCO₂/PaCO₂;     -   Difference of gastric-arterial or systemic-regional pH (pHgap),         from the logarithm of the ratio between the PgCO₂ and the         measured PaCO₂, expressed by the formula         pHgap=log PgCO₂/PaCO₂;     -   Standard intramucosal pH (pHis), from the difference between the         normal arterial pH and the logarithm of the ratio between the         PgCO₂ and the PaCO₂ measured, the normal arterial pH being 7.4,         expressed by the formula         pHis=7.4−log PgCO₂/PaCO₂;     -   Gradient of gastric-arterial or systemic-regional CO₂ in         percentage (% CO₂gap), from the ratio between: the difference         between the PgCO₂ and the PaCO₂ measured, and the PgCO₂,         multiplied by 100, expressed by the formula         % CO₂gap=(PgCO₂−PaCO₂)*100/PgCO₂.

By requiring a blood sample to obtain the arterial pH (pHa) and the CO₂ arterial pressure (PaCO₂), these parameters can not be calculated continuously, but our invention offers in real time an update of these parameters with the changes in the gastric measurement (PgCO₂), using the values of the latest blood sample. The entering of the pH and PaCO₂ blood values can be performed manually (without communication) or automatedly. This latter form has the advantage of saving time, and also improves the accuracy when performing data entry in real time, avoiding oversights or delays in the entry thereof.

As it can be seen, with these simplified equations all the regional parameters are calculated using parameters measured directly and not previously calculated (as bicarbonate or pHi). Moreover, the use of constants, which may vary with temperature changes or another one, is eliminated.

Although the CO₂ gradient (CO₂gap) has been appreciated as the key parameter in the monitoring of the splanchnic perfusion by some authors (17, 18), it has in our opinion a serious disadvantage that has provably caused the tonometric technique to fall into disuse: the interpretation of its values depends on the level of arterial PCO₂. Thus, it is not possible to establish a range of normality for this parameter, since this range will vary with the changes in the PaCO₂. For this reason, in the present system said parameter has been substituted by the % CO₂gap, which like the pHgap and the pHis, takes into account the level of the PaCO₂ (FIG. 2).

-   -   Calculations for continuous monitoring of the splanchnic         perfusion: the measurements obtained by the devices (a) and (c)         are used:     -   CO₂ gastric-transcutaneous or transcutaneous-regional gradient         in percentage, from the ratio between:     -   the difference between the PgCO₂ and the PtcCO₂, and     -   the PgCO₂,

multiplied by 100, expressed by the formula % CO₂gap(tc)=(PgCO₂−PtcCO₂)*100/PgCO₂;

-   -   Difference of gastric-transcutaneous or transcutaneous-regional         pH, from the logarithm of the ratio between the PgCO₂ and the         PtcCO₂, expressed by the formula         pHgap(tc)=log PgCO₂/PtcCO₂; and     -   Transcutaneous standard intramucosal pH, from the difference         between the normal arterial pH (7.4) and the logarithm of the         ratio between the PgCO₂ and the PtcCO₂, expressed by the formula         pHis(tc)=7.4−log PgCO₂/PtcCO₂.

The introduction of the normal pH constant allows the obtainment of values in the pH scale easy to interpret.

-   -   Intermittent calculation of the pulmonary physiological dead         space: the measurements obtained by the devices (b) and (d) are         used:     -   Difference of arterial-expiratory pH, from the logarithm of the         ratio between the PaCO₂ and the EtCO₂, expressed by the formula         pHgap(a-et)=log PaCO₂/EtCO₂; and     -   Arterial-expiratory standard pH, from the difference between the         normal arterial pH and the logarithm of the ratio between the         measured PaCO₂ and the EtCO₂, expressed by the formula         pHs(a-et)=7.4−log PaCO₂/EtCO₂.

It should be noted that our system also makes it possible to perform the exact calculation of the pulmonary physiological dead space (V_(D)/V_(T)), expressed by the formula (PaCO₂−PECO₂)/PaCO₂. For this purpose, the use of the mean expiratory CO₂ (PECO₂) instead of the EtCO₂ is required. For measurement thereof, the exhaled CO₂ sensor/probe (device d) must be removed from the patient's airway and introduced in a sealed manner in a large bag that receives all the expiratory air from the patient. These measurements are usually performed in the critically ill patient, who is usually intubated, so the expiratory gas collection is simple (the bag is connected to the expiratory gas outlet of the mechanical ventilator). However, it can only be performed when intermittent flow mechanical ventilators (MV) and in controlled mode (CMV) are used, since in SIMV modes, the constant basic flow of the MV will contaminate the sample in the bag. Neither is its measurement possible in the neonatal field due to the systematic use of continuous flow MV at these ages. On the other hand, it is difficult to achieve the sealing of the bag, which can cause inaccurate measurements due to the high diffusivity of CO₂. This is the reason why the present invention suggests the parameters pHgap(a-et) and pHs(a-et), that have not been described so far, since they use EtCO₂, avoiding the disadvantages of the measurement of the PECO₂. These calculations, even though they do not exactly measure the V_(D)/V_(T), can be useful to assess the variations thereof in the critically ill patient. Probably, these variations can also be assessed if we substitute the PECO₂ by the EtCO₂ in the calculation equation of the V_(D)/V_(T). This variant of calculation of the V_(D)/V_(T) is the one our system usually provides, when the CO₂ sensor/probe (device d) is positioned in the patient's airway.

-   -   Calculations for the continuous assessment of the pulmonary         physiological dead space: the measurements obtained by the         devices (c) and (d) are used:     -   Transcutaneous pulmonary physiological dead space, from the         ratio between:     -   the difference between the PtcCO₂ and the EtCO₂, and     -   the PtcCO₂, expressed by the formula         V_(D)/V_(T)(tc)=(PtcCO₂−EtCO₂)/PtcCO₂;     -   Difference of transcutaneous-expiratory pH, from the logarithm         of the ratio between the PtcCO₂ and the EtCO₂, expressed by the         formula         pHgap(tc-et)=log PtcCO₂/EtCO₂; and     -   Transcutaneous-expiratory standard pH, from the difference         between the normal arterial pH (7.4) and the logarithm of the         ratio between the PtcCO₂ and the EtCO₂, expressed by the formula         pHs(tc-et)=7.4−log PtcCO₂/EtCO₂.

For the continuous assessment of the VD/VT (VD/VT(tc)), the use of EtCO₂ instead of the PECO₂ is proposed herein. For the reasons set forth above, we sacrifice accuracy for convenience. While not providing exact values, we believe that it will allow proper assessment of the changes in this parameter. However, to obtain accurate measurements it is enough to change the position of the CO₂ sensor, as we have already discussed.

In another preferred embodiment, the computer program (f5) also estimates also the following parameters related to the continuous measurement of the splanchnic tissue perfusion, from the measurements obtained by the devices (a) and (d):

-   -   Gastric-expiratory or expiratory-regional CO₂ gradient in         percentage, from the ratio between:     -   the difference between the PgCO₂ and the EtCO₂, and     -   the PgCO₂,

multiplied by 100, expressed by the formula % CO₂gap(et)=(PgCO₂−EtCO₂)*100/PgCO₂;

-   -   Difference of gastric-expiratory or expiratory-regional pH, from         the logarithm of the ratio between the PgCO₂ and the EtCO₂,         expressed by the formula         pHgap(et)=log PgCO₂/EtCO₂; and     -   expiratory standard intramucosal pH, from the difference between         the normal arterial pH (7.4) and the logarithm of the ratio         between the PgCO₂ and the EtCO₂, expressed by the formula         pHis(et)=7.4−log PgCO₂/EtCO₂.

The parameters described have the advantage, over the classical parameters, of not requiring the extraction and analysis of blood samples for the calculation thereof and, with it, they can be obtained in an automated and continuous way.

Preferably, the device (f) of reception, conversion, storage, integration, processing, management and display of the information is a personal computer.

The present invention relates also to the use of the device described for measuring, recording and monitoring the splanchnic tissue perfusion and the pulmonary physiological dead space in a continuous, real time and automated way. Said measurement, said recording and said monitoring comprise at least the following steps:

-   -   1) measuring the PgCO₂ by the device (a) of continuous measuring         of the carbonic anhydride pressure in the lumen of the digestive         tube;     -   2) measuring the pHa and the PaCO₂ on a blood sample by the         device (b) of intermittent measuring of the arterial pH and the         CO₂ arterial pressure;     -   3) measuring the PtcCO₂ by the device (c) of continuous         measuring of the CO₂ transcutaneous pressure;     -   4) measuring the EtCO₂, by the device (d) of continuous         measuring of the end-expiratory CO₂;     -   5) transferring the data of the measurements obtained from the         measuring devices (a, b, c and d) to the device (f) of         reception, conversion, storage, integration, processing,         management and display of said data through the connections (e);     -   6) converting the data transferred to the device (f) of         reception, conversion, storage, integration, processing,         management and display of the measurements by the         conversion-normalization module (f2),     -   7) processing and integrating the data converted-normalized in         the prior step by the module (f3) of processing and integration         of the data,     -   8) entering commands in the device (f) of reception, conversion,         storage, integration, processing, management and display of said         data, and estimating and viewing in an automated, continuous and         real time way the parameters related to the measurement of the         splanchnic tissue perfusion and the pulmonary physiological dead         space, by the computer program (f5), the input interface (f6)         and the output interface (f7).

Preferably, the measurement of step 1) is performed either in the stomach or in the sigmoidal colon, using the probe with optic fibre sensor or with an already described terminal silicone balloon.

Also preferably, when the measurement of step 1) is carried out in the stomach, the acid secretion of said organ must be inhibited by administering one of the compounds selected from anti-H₂ and proton pump inhibitors, to increase the reliability of the measurement.

In a preferred embodiment, in step 3) the device (c) is calibrated “in vivo” at the beginning of the measuring entering a PaCO₂ value of a blood sample.

In another preferred embodiment, the PECO₂ is measured in step 4) by a large bag wherein the expiratory gas is accumulated and the CO₂ Pressure of said gas is determined in said bag by the CO₂ probe/sensor of the device d, which is located in the bag in a sealed way.

The scope of application of the monitoring system proposed is exclusively the hospital:

1) Critically ill patients admitted to ICU and resuscitation units: the pHi has shown to be a sensitive but little specific prognostic indicator in the critically ill patient, having shown its usefulness as a multiple organ failure and death predictor in multiple situations, both in the adult and the pediatric patient. Thus, its prognostic usefulness has shown itself to be superior to that of the hemodynamic and systemic oxygenation variables. Its use in interventionist studies to guide the therapy is, however, controversial. Thus, while Gutierrez et al (19) and Ivatury et al (20) observed how the therapy guided by the pHi improved the prognosis of the patients, Gomersall et al (21), did not find any benefit in the group whose therapy was guided by means of the pHi. The limitations of the technique described could explain this deficit. The improvements achieved with the present invention provide the tool necessary to direct the therapy in these patients.

2) The patient undergoing cardiovascular surgery or major surgery, thoracic and abdominal, including liver, intestinal (detection of celiac and mesenteric ischemia) and lung transplant: various studies suggest that the sigmoidal tonometry can be useful to predict the occurrence of ischemic cholitis secondary to tissue hypoxia, main cause of morbidity and mortality after major abdominal vascular surgery. Likewise, the hypoperfusion of the colon detected by tonometry, can be associated to endotoxemia and release of cytokines, which may condition the evolution to MOF and death.

3) Diagnostic assay of celiac and mesenteric symptomatic vascular disease that allows the prediction of the usefulness of surgery.

4) Assessment of the alterations in the ventilation-perfusion in the critically ill patient. These alterations are very frequent in this type of patients, particularly when the pulmonary blood flow decreases (e.g., situations of shock, pulmonary embolism, cardiopulmonary resuscitation), when the alveoli are overdistended by positive pressure ventilation and when the alveolo-capillary interface is destroyed (e.g., emphysema).

The invention described herein presents the following advantages over other systems known in the field of the art:

1. Uses for obtaining the measurements clinical equipment commercially available from different manufacturers. Therefore, the dependence on a single manufacturer is avoided. Moreover, the user will be able to simplify the acquisition of the present system if he uses the measuring equipment available at his Centre. It will also be possible to continue using this equipment independently of the present invention. At the same time, the system will allow all the technological improvements that may be marketed for making measurements of parameters to be incorporated. In this sense, if devices such as Paratrend or other similar ones for continuous measuring of the pHa and the PaCO₂ were marketed again, the now intermittent calculations will be able to be carried out continuously.

2. Intermittent monitoring of the splanchnic perfusion:

-   -   In addition to pHi, it provides the calculation of other         classical parameters such as pHgap and pHis. These two         parameters, although described in the literature, have not been         provided by any marketed equipment.     -   For the calculation of all the regional parameters their         simplified equations are used, only using the parameters         measured directly. In this way, interference from previous         calculations and changes in the constants of the standard         formulae are eliminated.     -   Substitutes the calculation of the CO₂gap, having serious         disadvantages, by a new parameter, % CO₂gap, overcoming these         limitations.     -   For these intermittent calculations, the introduction of         measurements derived from blood samples is required. These data         can be entered manually (like in other marketed devices) or         automatically through the connection with the communications         port of the pH and gas analyzer. This latter form has the         advantage of saving time for the health care provider, and also         improving the accuracy by performing the data entry in real         time, avoiding oversights or delays in the entry.     -   Although the parameters requiring a blood sample can only be         determined intermittently, the present invention offers, in real         time, an update of these parameters with the changes of the         gastric measurement (PgCO₂), using the values of the latest         blood sample.

3. Continuous monitoring of the splanchnic perfusion:

-   -   Through the measurements of PgCO₂ and PtcCO₂ obtained from         marketed equipment, the present equipment performs the automated         and continuous calculation of new regional parameters, not         described so far, of easy clinical interpretation, with ranges         of normality fixed and independent of the CO₂ blood values. The         PtcCO₂ had not been used previously for this purpose.     -   Provides other regional parameters of continuous measuring not         described until now through the integration of the measurements         of PgCO₂ and EtCO₂.     -   Improves the health care activity by displaying the information         continuously and in real time.     -   Decreases the consumption of time by the health care provider         and improves the accuracy of the information stored, by carrying         out all the functions automatedly.

4. Intermittent and continuous monitoring of the pulmonary physiological dead space: It integrates the measurement of the CO₂ exhaled with the PaCO₂ for intermittent monitoring, and with the PtcCO₂ for continuous monitoring, of the alterations in the pulmonary physiological dead space by calculating the V_(D)/V_(T) and the other derived parameters not described so far. This type of monitoring, that allows assessment of alterations in the pulmonary ventilation/perfusion ratio, is currently not provided by any marketed equipment.

5. The information is displayed in tabular and graphic form, easy to be interpreted by clinicians. It assesses the evolution over time by depicting a trends graph.

6. It is provided with an operating alarm system (problem with the reception of the measurements as disconnections, etc.) and a programmable clinical alarm (measurement values exceeded).

7. It saves the information in databases, so that the same can be subsequently recovered.

Therefore, the invention herein described integrates measurements performed by clinical equipment that has not been used previously for this purpose (as the transcutaneous capnograph), to provide in a continuous and automated way new parameters useful for the estimate of the splanchnic perfusion-oxygenation and the pulmonary physiological dead space that are currently not provided by any other marketed system.

ABBREVIATIONS OF THE FIELD OF THE ART

-   -   ATP, adenosine triphosphate     -   CO₂gap or P(g-a)CO₂, gastric-arterial or systemic-regional CO₂         gradient (=PgCO₂−PaCO₂)     -   CO₂gap(et) or P(g-Et)CO₂, gastric-expiratory or         expiratory-regional CO₂ gradient (=PgCO₂−EtCO₂)     -   % CO₂gap, gastric-arterial or systemic-regional CO₂ gradient in         percentage (=(PgCO₂−PaCO₂)*100/PgCO₂)     -   % CO₂gap(et), gastric-expiratory or expiratory-regional CO₂         gradient in percentage (=(PgCO₂−PetCO₂)*100/PgCO₂)     -   % CO₂gap(tc), gastric-transcutaneous or transcutaneous-regional         CO₂ gradient in percentage (=(PgCO₂−PtcCO₂)*100/PgCO₂)     -   EtCO₂, end-expiratory carbonic anhydride pressure     -   [HCO₃ ⁻], bicarbonate concentration     -   PaCO₂, arterial carbonic anhydride pressure     -   PECO₂, mean expiratory carbonic anhydride pressure     -   PgCO₂, carbonic anhydride pressure in the lumen of the digestive         tube (usually in the stomach, but also in the sigmoidal colon)     -   pHa, arterial pH     -   pHgap, difference of gastric-arterial or systemic-regional pH         (=pHa−pHi; it can also be calculated by the simplified         equation=log PgCO₂/PaCO₂)     -   pHgap(a-et), difference of the arterial-expiratory pH (=log         PaCO₂/EtCO₂)     -   pHgap(et), difference of the gastric-expiratory or         expiratory-regional pH (=log PgCO₂/EtCO₂)     -   pHgap(tc), difference of gastric-transcutaneous or         transcutaneous-regional pH (=log PgCO₂/PtcCO₂)     -   pHgap(tc-et), difference of transcutaneous-expiratory pH (=log         PtcCO₂/EtCO₂)     -   pHi, intramucosal pH in the digestive tube (usually gastric, but         also in the sigmoidal colon) (=6.1+log 10([HCO3⁻PgCO₂*0.03); it         can also be calculated by the simplified equation=pHa−log         PgCO₂/PaCO₂)     -   pHis, standard intramucosal pH (=7.4−pHgap; it can also be         calculated by the simplified equation=7.4−log PgCO₂/PaCO₂)     -   pHis(et), expiratory standard intramucosal pH (=7.4−log         PgCO₂/EtCO₂)     -   pHis(tc), transcutaneous standard intramucosal pH (=7.4−log         PgCO₂/PtcCO₂)     -   pHs(a-et), arterial-expiratory standard pH (=7.4−log         PaCO₂/EtCO₂)     -   pHs(tc-et), transcutaneous-expiratory standard pH (=7.4−log         PtcCO₂/EtCO₂)     -   PaO₂, oxygen arterial pressure     -   PtcCO₂, CO₂ transcutaneous pressure     -   ARDS, acute respiratory distress syndrome     -   PSS, physiological saline serum     -   V_(D)/V_(T), pulmonary physiological dead space         (=(PaCO₂−PECO₂)/PaCO₂)     -   V_(D)/V_(T)(tc), transcutaneous pulmonary physiological dead         space (=(PtcCO₂−EtCO₂)/PtcCO₂)

BIBLIOGRAPHY

-   1. Fiddian-Green R G. Gastric intramucosal pH, tissue oxygenation     and acid-base balance. Br. J. Anaesth. 1995; 74: 591-606 -   2. Fiddian-Green R G. Tonometry: theory and applications. Intensive     Care World 1992; 9: 60-65 -   3. Pinsky M R, Schlichtig R. Regional oxygen delivery in oxygen     supply-dependent states. Intensive Care Med. 1990; 16: S169-171 -   4. Hartmann M, Montgomery A, Jonsson K, et al. Tissue oxygenation in     hemorrhagic shock measured as transcutaneous oxygen tension,     subcutaneous oxygen tension, and gastrointestinal intramucosal pH in     pigs. Crit. Care Med 1991; 19: 205-210 -   5. Schlichting E, Lyberg T. Monitoring of tissue oxygenation in     shock: an experimental study in pigs. Crit. Care Med 1995; 23:     1703-1710 -   6. Antonson J B, Boyle C C, Kurithoff K L, et al. Validation of     tonometric measurement of intramural pH during endotoxemia and     mesenteric occlusion in pigs. Am J Physiol 1990; 259: G519-523 -   7. Boda D, Muranyi L. “Gastrotonometry”. An aid to the control of     ventilation during artificial respiration. Lancet 1959; 273: 181-182 -   8. Bergofsky E H. Determination of tissue O₂ tensions by hollow     visceral tonometers: effect of breathing enriched O₂ mixtures. J     Crit. Invest 1964; 43: 193-200 -   9. Dawson A M. Small bowel tonometry: assessment of small gut     mucosal oxygen tension in dog and man. Nature 1965; 206: 943-944 -   10. Fiddian-Green R G, Pittenger G, Whitehouse W M. Back-diffusion     of CO₂ and its influence on the intramural pH in gastric mucosa. J     Surg Res 1982; 33: 39-48 -   11. Clark C H, Gutierrez G. Gastric intramucosal pH: a noninvasive     method for the indirect measurement of tissue oxygenation. Am J     Critical Care 1992; 2: 53-60 -   12. Kolkman J J, Otte J A, Groeneveld B J. Gastrointestinal luminal     PCO₂ tonometry: an update on physiology, methodology and clinical     applications. Br J Anaesth 2000; 84: 74-86 -   13. Calvo C, Ruza F, López-Herce J, et al. Usefulness of gastric     intramucosal pH for monitoring hemodynamic complications in     critically ill children. Intensive Care Med 1997 23: 1268-1274 -   14. Noone R B, Mythen M G, Vaslef S N. In vitro validation of an     automated on-line gastrointestinal tonometer (the Tonocap). Crit.     Care Med 1997; 25(1S): A137 -   15. Barry B, Mallick A, Hartley G, et al. Comparison of air     tonometry with gastric tonometry using saline and other     equilibrating fluids: an in vivo and in vitro study. Intensive Care     Med 1998; 24: 777-784 -   16. Janssens U, Graf J, Koch K C, et al. Gastric tonometry: in vivo     comparison of saline and air tonometry in patients with cardiogenic     shock. Br J Anaesth 1998; 81: 676-680 -   17. Schlichtig R, Mehta N, Gayowki T J P, et al. Tissue-arterial     PCO2 difference is a better marker of ischemia than intramural     pH(pHi) or arterial pH-pHi difference. J Crit. Care 1996; 11: 51-56 -   18. Vincent J L. Gastric mucosal pH is definitely obsolete. Please     tell us more about gastric mucosal PCO2. Crit. Care Med 1998; 26:     1479-1480 -   19. Gutierrez G, Palizas F, Doglio G, et al. Gastric intramucosal pH     as a therapeutic index of tissue oxygenation in critically ill     patients. Lancet 1992; 339: 195-199 -   20. Ivatury R R, Simon R J, Islam S, et al. A prospective randomized     study of end points of resuscitation after major trauma: global     oxygen transport indices versus organ-specific gastric mucosal pH. J     Am Coll Surg 1996; 183: 145-154 -   21. Gomersall C D, Joint G M, Freebairn R C, et al. Resuscitation of     critically ill patients based on the results of gastric tonometry: a     prospective, randomized, controlled trial. Crit. Care Med 2000; 28:     607-614

FIGURES

FIG. 1. Scheme of the system for measuring, recording and monitoring the splanchnic tissue perfusion and the pulmonary physiological dead space in an automated way, both continuously and intermittently, and in real time (pH-Tone instrument).

1. Critically ill patient in: intensive care, resuscitation or operating room.

2. Clinical equipment (a) for the measurement of the PgCO₂:

-   -   2.1. General Electric M-Tone Module     -   2.2. Instrument of the Institute of Chemical Process Development         and Control     -   2.3. Other

3. Standard blood pH and gas analyzer (b): intermittent measurement of pHa and PaCO₂ (multiple manufacturers).

4. Clinical equipment (c) for the measurement of the PtcCO₂: Radiomether “Tosca” oxycapnograph, Sentect oxycapnograph or other transcutaneous capnographs.

5. Clinical equipment (d) for the measurement of the EtCO₂ and the PECO₂ (multiple manufacturers).

6. Device (f) of reception, conversion, storage, integration, processing, management and display of the data recorded in the measurements.

Calculation of Derived Parameters: measuring device (a)+measuring device (b)=Intermittent monitoring of the splanchnic perfusion. measuring device (a)+measuring device (c)=Continuous monitoring of the splanchnic perfusion. measuring device (b)+measuring device (d)=Intermittent monitoring of the pulmonary physiological dead space. measuring device (c)+measuring device (d)=Continuous monitoring of the pulmonary physiological dead space.

FIG. 2. Variation of the % CO₂gap, pHis and pHgap at different levels of PaCO₂ with a constant CO₂gap of 10 mmHg. As it can be seen, a CO₂gap of 10 mmHg is pathological when the arterial CO₂ level is normal or low, but not when this is high. Therefore, the interpretation of its values depends on the level of the arterial PCO₂ and it is not possible to establish a normal range for this parameter, since it varies with the values of the PaCO₂. It is also not possible to compare series of patients since the meaning of a certain value of CO₂gap is to be varied as a function of the level of PaCO₂ that each patient had. In the inventors' opinion, and contrary to the opinion of other authors (17, 18), this fact seriously limits the usefulness of this parameter, where the % CO₂gap, the pHis or the pHgap should be preferably used.

FIG. 3. Illustrative scheme of a patient in intensive care, resuscitation or operating room with a tonometry probe for the measurement of PgCO₂ and a sensor for the earlobe for the measurement of PtcCO₂. The probe for the measurement of EtCO₂ is found at the end of the endotracheal tube.

1. Intubated patient.

2. Sonometric probe for the measurement of PgCO₂.

4. Sensor for the earlobe for the measurement of PtcCO₂.

5. EtCO₂ measuring probe.

7. Endotracheal tube (intubation).

FIG. 4. Simulation of the output interface (f7) of the device (f) of reception, conversion, storage, integration, processing, management and display of the data recorded in the measurements, allowing the user to view in real time the information input in the device (f) and output from the computer module (f5), in both tabular and graphic form. Observe the graphs of continuous monitoring of the pHis and CO₂gap, in its two forms of calculation (tc) and (et).

FIG. 5. 48 hours evolution of the standard pHi (pHis) in its three forms of calculation in a patient with ARDS:

-   -   pHis Sample: calculated intermittently with the measurement of         the PaCO₂ obtained from a blood sample.     -   pHis(tc): determined in a continuous and automated way with the         measurement of the transcutaneous CO₂ (present invention).     -   pHis(et): determined in a continuous and automated way with the         measurement of the CO₂ exhaled (present invention).

Observe the perfect correlation between the pHis calculated with blood sample and transcutaneous sample, and the important differences of both with the pHis(et). These differences can be attributed to variations in the pulmonary ventilation and perfusion. For these measurements, no previous calibration of the PtcCO₂ was performed with a measurement of the PaCO₂. With this calibration, the correlation between the pHis and the pHis(tc) is still further improved. 

The invention claimed is:
 1. A system for measuring, recording, and monitoring splanchnic tissue perfusion and pulmonary physiological dead space, comprising: a) a continuous measuring device of carbonic anhydride pressure in a lumen of a digestive tube (PgCO₂), comprising a probe configured to be positioned nasogastrically or recto-sigmoidally, the probe type for measuring the CO₂ being selected from the group consisting of: a probe with a terminal silicone balloon permeable to CO₂ that is filled with air, which measures CO₂ by extraction, analysis, and reintroduction of a gas sample in the balloon every 10 minutes and automatedly; and a probe with a optic fiber sensor in its patient end, measuring CO₂ in situ and continuously; b) a standard intermittent measuring device of the arterial pH, pHa, and CO₂ arterial pressure, PaCO₂, of a blood sample; c) a continuous measuring device of CO₂ transcutaneous pressure, PtcCO₂, consisting of a transcutaneous capnography sensor; d) a continuous measuring device of end-expiratory CO₂, EtCO₂, consisting of an expiratory air standard capnograph, the probe or sensor of which is connected in a patient's airway; e) connections between the measuring devices (a, b, c and d); and f) a device of reception, conversion, storage, integration, processing, management, and display of the data recorded in the measuring devices (a, b, c and d) comprising: a computer program module (f1) of reception and storage of the measurements performed with the measuring devices (a, b, c and d), a second specific module (f2) of conversion-normalization of data received and stored in the reception and storage module (f1), a third module (f3) of processing and integration of the data converted-normalized by the conversion-normalization module (f2), a fourth program module (f4) of storage of the data processed by the processing module (f3); a fifth specific module (f5) of automated, continuous, and real time estimate of the following parameters related to the measurement of the splanchnic tissue perfusion and the pulmonary physiological dead space, the data being derived from the fourth storage module (f4) that was previously processed by the processing module (f3): intramucosal pH in the digestive tube, pHi, which is estimated as a function of the pHa and the PaCO₂ obtained by the device (b), and the PgCO₂ obtained by the device (a); difference of gastric-arterial or systemic-regional pH, pHgap, which is estimated as a function of the PgCO₂ obtained by the device (a) and the PaCO₂ obtained by the device (b); standard intramucosal pH, pHis, which is estimated as a function of the normal arterial pH, the PgCO₂ obtained by the device (a) and the PaCO₂ obtained by the device (b), the normal arterial pH being 7.4; gastric-arterial CO₂ gradient in percentage, % CO₂gap, which is estimated as a function of the PgCO₂ obtained by the device (a) and the PaCO₂ obtained by the device (b); difference of gastric-transcutaneous pH, pHgap(tc), which is estimated as a function of the PgCO₂ obtained by the device (a) and the PtcCO₂ obtained by the device (c); transcutaneous standard intramucosal pH, pHis(tc), which is estimated as a function of the normal arterial pH (7.4), the PgCO₂ obtained by the device (a) and the PtcCO₂ obtained by the device (c); gastric-transcutaneous CO₂ gradient in percentage, % CO₂gap(tc), which is estimated as a function of the PgCO₂ obtained by the device (a) and the PtcCO₂ obtained by the device (c); difference of arterial-expiratory pH, pHgap(a-et), which is estimated as a function of the PaCO₂ obtained by the device (b) and the EtCO₂ obtained by the device (d); arterial-expiratory standard pH, pHs(a-et), which is estimated as a function of the normal arterial pH (7.4), the PaCO₂ obtained by the device (b) and the EtCO₂ obtained by the device (d); pulmonary physiological dead space, V_(D)/V_(T), which is estimated as a function of the PaCO₂ obtained by the device (b) and the PECO₂ obtained by the device (d); transcutaneous pulmonary physiological dead space, V_(D)/V_(T)(tc), which is estimated as a function of the PtcCO₂ obtained by the device (c) and the EtCO₂ obtained by the device (d); difference of transcutaneous-expiratory pH, pHgap(tc-et), which is estimated as a function of the PtcCO₂ obtained by the device (c) and the EtCO₂ obtained by the device (d); and transcutaneous-expiratory standard pH, pHs(tc-et), which is estimated as a function of the normal arterial pH, the PtcCO₂ obtained by the device (c) and the EtCO₂ obtained by the device (d); an input interface (f6) allowing a user to enter commands in the fifth specific module (f5) of parameter estimation; an output interface (f7) allowing the user to view in real time the information input in the device (f) and the output from the fifth specific module (f5), in both tabular and graphic form; a module (f8) of recording the parameters estimated by the fifth specific module (f5), for the subsequent recovery and analysis thereof; and an alarm (f9) for checking the operation of the device (f) and the connections (e), to detect problems in operating and receiving measurements, and parameters programmable alarm (measurement values exceeded) by the fifth specific module (f5), independent of the one existing in the measuring equipment.
 2. The system according to claim 1, wherein the probe of the device (a) is configured to be in the stomach or in the recto-sigmoidal colon.
 3. The system according to claim 2, wherein the transcutaneous capnography sensor of the device (c) is a transcutaneous oxycapnograph for the earlobe, which can be used in patients of any age.
 4. The system according to claim 2, wherein the computer program (f5) of parameter estimates performs the following estimates: pHi, from the difference between the pHa obtained by the device (b) and the logarithm of the ratio between the PgCO₂ obtained by the device (a) and the PaCO₂ obtained by the device (b); pHgap, from the logarithm of the ratio between the PgCO₂ obtained by the device (a) and the PaCO₂ obtained by the device (b); pHis, from the difference between the normal arterial pH and the logarithm of the ratio between the PgCO₂ obtained by the device (a) and the PaCO₂ obtained by the device (b), the normal arterial pH being 7.4, % CO₂gap, from the ratio between: the difference between the PgCO₂ obtained by the device (a) and the PaCO₂ obtained by the device (b), and the PgCO₂, multiplied by 100; % CO₂gap(tc), from the ratio between: the difference between the PgCO₂ obtained by the device (a) and the PtcCO₂ obtained by the device (c), and the PgCO₂, multiplied by 100; pHgap(tc), from the logarithm of the ratio between the PgCO₂ obtained by the device (a) and the PtcCO₂ obtained by the device (c); pHis(tc), from the difference between the normal arterial pH (7.4) and the logarithm of the ratio between the PgCO₂ obtained by the device (a) and the PtcCO₂ obtained by the device (c); pHgap(a-et), from the logarithm of the ratio between the PaCO₂ measured with the device (b) and the EtCO₂ obtained by the device (d); pHs(a-et), from the difference between the normal arterial pH (7.4) and the logarithm of the ratio between the PaCO₂ measured by the device (b) and the EtCO₂ obtained by the device (d); V_(D)/V_(T)(tc), from the ratio between: the difference between the PtcCO₂ obtained by the device (c) and the EtCO₂ obtained by the device (d), and the PtcCO₂; pHgap(tc-et), from the logarithm of the ratio between the PtcCO₂ obtained by the device (c) and the EtCO₂ obtained by the device (d); and pHs(tc-et), from the difference between the normal arterial pH (7.4) and the logarithm of the ratio between the PtcCO₂ obtained by the device (c) and the EtCO₂ obtained by the device (d).
 5. The system according to claim 2, wherein the device (d) further measures the mean CO₂ expiratory pressure, PECO₂, placing the expiratory CO₂ sensor/probe inside a sealed bag placed in the expiratory outlet of the mechanical ventilator, and calculates the pulmonary physiological dead space, V_(D)/V_(T), from the ratio between: the difference between the PaCO₂ obtained by the device (b) and the PECO₂ obtained by the device (d), and the PaCO₂.
 6. The system according to claim 1, wherein the transcutaneous capnography sensor of the device (c) is a transcutaneous oxycapnograph for the earlobe, which can be used in patients of any age.
 7. The system according to claim 6, wherein the computer program (f5) of parameter estimates performs the following estimates: pHi, from the difference between the pHa obtained by the device (b) and the logarithm of the ratio between the PgCO₂ obtained by the device (a) and the PaCO₂ obtained by the device (b); pHgap, from the logarithm of the ratio between the PgCO₂ obtained by the device (a) and the PaCO₂ obtained by the device (b); pHis, from the difference between the normal arterial pH and the logarithm of the ratio between the PgCO₂ obtained by the device (a) and the PaCO₂ obtained by the device (b), the normal arterial pH being 7.4, % CO₂gap, from the ratio between: the difference between the PgCO₂ obtained by the device (a) and the PaCO₂ obtained by the device (b), and the PgCO₂, multiplied by 100; % CO₂gap(tc), from the ratio between: the difference between the PgCO₂ obtained by the device (a) and the PtcCO₂ obtained by the device (c), and the PgCO₂, multiplied by 100; pHgap(tc), from the logarithm of the ratio between the PgCO₂ obtained by the device (a) and the PtcCO₂ obtained by the device (c); pHis(tc), from the difference between the normal arterial pH (7.4) and the logarithm of the ratio between the PgCO₂ obtained by the device (a) and the PtcCO₂ obtained by the device (c); pHgap(a-et), from the logarithm of the ratio between the PaCO₂ measured with the device (b) and the EtCO₂ obtained by the device (d); pHs(a-et), from the difference between the normal arterial pH (7.4) and the logarithm of the ratio between the PaCO₂ measured by the device (b) and the EtCO₂ obtained by the device (d); V_(D)/V_(T)(tc), from the ratio between: the difference between the PtcCO₂ obtained by the device (c) and the EtCO₂ obtained by the device (d), and the PtcCO₂; pHgap(tc-et), from the logarithm of the ratio between the PtcCO₂ obtained by the device (c) and the EtCO₂ obtained by the device (d); and pHs(tc-et), from the difference between the normal arterial pH (7.4) and the logarithm of the ratio between the PtcCO₂ obtained by the device (c) and the EtCO₂ obtained by the device (d).
 8. The system according to claim 6, wherein the device (d) further measures the mean CO₂ expiratory pressure, PECO₂, placing the expiratory CO₂ sensor/probe inside a sealed bag placed in the expiratory outlet of the mechanical ventilator, and calculates the pulmonary physiological dead space, V_(D)/V_(T), from the ratio between: the difference between the PaCO₂ obtained by the device (b) and the PECO₂ obtained by the device (d), and the PaCO₂.
 9. The system according to claim 1, wherein the fifth specific module (f5) of parameter estimates performs the following estimates: pHi, from the difference between the pHa obtained by the device (b) and the logarithm of the ratio between the PgCO₂ obtained by the device (a) and the PaCO₂ obtained by the device (b); pHgap, from the logarithm of the ratio between the PgCO₂ obtained by the device (a) and the PaCO₂ obtained by the device (b); pHis, from the difference between the normal arterial pH and the logarithm of the ratio between the PgCO₂ obtained by the device (a) and the PaCO₂ obtained by the device (b), the normal arterial pH being 7.4, % CO₂gap, from the ratio between: the difference between the PgCO₂ obtained by the device (a) and the PaCO₂ obtained by the device (b), and the PgCO₂, multiplied by 100; % CO₂gap(tc), from the ratio between: the difference between the PgCO₂ obtained by the device (a) and the PtcCO₂ obtained by the device (c), and the PgCO₂, multiplied by 100; pHgap(tc), from the logarithm of the ratio between the PgCO₂ obtained by the device (a) and the PtcCO₂ obtained by the device (c); pHis(tc), from the difference between the normal arterial pH (7.4) and the logarithm of the ratio between the PgCO₂ obtained by the device (a) and the PtcCO₂ obtained by the device (c); pHgap(a-et), from the logarithm of the ratio between the PaCO₂ measured with the device (b) and the EtCO₂ obtained by the device (d); pHs(a-et), from the difference between the normal arterial pH (7.4) and the logarithm of the ratio between the PaCO₂ measured by the device (b) and the EtCO₂ obtained by the device (d); V_(D)/V_(T)(tc), from the ratio between: the difference between the PtcCO₂ obtained by the device (c) and the EtCO₂ obtained by the device (d), and the PtcCO₂; pHgap(tc-et), from the logarithm of the ratio between the PtcCO₂ obtained by the device (c) and the EtCO₂ obtained by the device (d); and pHs(tc-et), from the difference between the normal arterial pH (7.4) and the logarithm of the ratio between the PtcCO₂ obtained by the device (c) and the EtCO₂ obtained by the device (d).
 10. The system according to claim 9, wherein the device (d) further measures the mean CO₂ expiratory pressure, PECO₂, placing the expiratory CO₂ sensor/probe inside a sealed bag placed in the expiratory outlet of the mechanical ventilator, and calculates the pulmonary physiological dead space, V_(D)/V_(T), from the ratio between: the difference between the PaCO₂ obtained by the device (b) and the PECO₂ obtained by the device (d), and the PaCO₂.
 11. The system according to claim 1, wherein the device (d) further measures mean CO₂ expiratory pressure, PECO₂, the expiratory CO₂ sensor/probe configured to be placed inside a sealed bag placed in the expiratory outlet of the mechanical ventilator, and calculates the pulmonary physiological dead space, V_(D)/V_(T), from the ratio between: the difference between the PaCO₂ obtained by the device (b) and the PECO₂ obtained by the device (d), and the PaCO₂.
 12. The system according to claim 1, wherein the connections (e) in the devices (a), (c) and (d) are made through the RS-232 serial ports, and the device (b) through its ethernet network connection.
 13. The system according to claim 1, wherein the fifth specific module (f5) further estimates the following parameters related to the continuous measurement of the splanchnic tissue perfusion: gastric-expiratory CO₂ gradient in percentage, % CO₂gap(et), from the ratio between: the difference between the PgCO₂ obtained by the device (a) and the EtCO₂ obtained by the device (d), and the PgCO₂, multiplied by 100; difference of expiratory-regional pH, pHgap(et), from the logarithm of the ratio between the PgCO₂ obtained by the device (a) and the EtCO₂ obtained by the device (d); and expiratory standard intramucosal pH, pHis(et), from the difference between the normal arterial pH and the logarithm of the ratio between the PgCO₂ obtained by the device (a) and the EtCO₂ obtained by the device (d), the normal arterial pH being 7.4.
 14. The system according to claim 1, wherein the device (f) of reception, conversion, storage, integration, processing, management and display of the information is a personal computer.
 15. A method for measuring, recording or monitoring the splanchnic tissue perfusion and the pulmonary physiological dead space in real time and in an automated way, either intermittently or continuously depending on the parameter to be measured, using the system defined in claim 1, wherein the method comprises the following steps: 1) measuring the PgCO₂ by the device (a) of continuous or automated measuring, every 10 minutes, of the carbonic anhydride pressure in the lumen of the digestive tube; 2) measuring the pHa and the PaCO₂ in a blood sample by the device (b) of intermittent measuring of the arterial pH and the CO₂ arterial pressure; 3) measuring the PtcCO₂ by the device (c) of continuous measuring of the CO₂ transcutaneous pressure; 4) measuring the EtCO₂, by the device (d) of continuous measuring of the end-expiratory CO₂; 5) transferring the data of the measurements obtained from the measuring devices (a, b, c and d) to the device (f) of reception, conversion, storage, integration, processing, management and display of said data through the connections (e); 6) converting-normalizing the data transferred to the device (f) of reception, conversion, storage, integration, processing, management and display of the measurements by the conversion-normalization module (f2), 7) processing and integrating the data converted-normalized in the prior step by the processing and integration module (f3), 8) entering commands in the device (f) of reception, conversion, storage, integration, processing, management and display of said data, and estimating and viewing in an automated, continuous and real time way the parameters related to the measurement of the splanchnic tissue perfusion and the pulmonary physiological dead space, by the computer program (f5), the input interface (f6) and the output interface (f7).
 16. The method according to claim 15, wherein the measurement of step 1) is performed in one of the organs selected from the group consisting of the stomach and the recto-sigmoidal colon.
 17. The method according to claim 16, wherein when the measurement of step 1) is carried out in the stomach, the acid secretion of said organ is inhibited by the administration of one of the compounds selected from anti-H₂ or proton pump inhibitors, to increase the reliability of the measurement.
 18. The method according to claim 15, wherein in step 3) the device (c) is calibrated in vivo at the beginning of the measuring entering a PaCO₂ value of a blood sample.
 19. The method according to claim 15, wherein in step 4) the PECO₂ is measured by the positioning of the expiratory CO₂ sensor/probe in a large sealed bag connected to the expiratory outlet of the mechanical ventilator, wherein the expiratory gas is accumulated, and the Pressure of said gas in said bag is determine. 